The prevalence of diabetes mellitus increases with age. While the mechanism by which age increases the risk of diabetes remain to be fully elucidate, the development of insulin resistance coupled with an inability to appropriately increase insulin secretion appears to play an important role. The present experiments will seek to determine whether the age associated decrease in circulating androgens contributes to the alterations in carbohydrate metabolism that are commonly observed in the elderly. To do so, the major determinants of glucose tolerance (e.g. insulin action, insulin secretion and glucose effectiveness) will be measured prior to and following one year of treatment with either gonadal (testosterone in men) or adrenal (dihydroepinadosterone in men and women) androgens in amounts designed to restore plasma levels to those typically observed in young (e.g. 20-30 years) healthy individuals. Results will be compared to those observed in a) matched elderly individuals treated with placebo for one year to control for time dependent changes; and b) gender matched young health subjects. Insulin action and glucose effectiveness will be measured using a modification of the insulin suppression test combined with the "cold" and "hot" minimal models. Insulin secretion will be measured following ingestion of a mixed meal from C-peptide data using a deconvolution approach. The postprandial pattern of carbohydrate metabolism will be measured using the dual isotope radio-labeled meal technique H13/C02 bicarbonate infusion and indirect calorimetry. Results will be interpreted in light of concomitant measures of body composition (percent body fat, visceral obesity, lean body mass), levels of fitness (V02 max, strength), fat metabolism (in collaboration with Dr. Jensen project 4) and protein metabolism (in collaboration with Dr. Nair in project 1). It is anticipated that the proposed studies, by defining the effects of androgen replacement on carbohydrate metabolism, will provide new insights regarding the potential benefits and risks of using these agents in the treatment of age related sarcopenia.